In Q1 2026, innovation in the autoimmune disease space has shifted from fragmented breakthroughs to systematic progress centered on a few core therapeutic targets. This article provides a target-driven overview of key business development (BD) deals and clinical milestones, highlighting the dominant trends shaping the autoimmune drug development landscape.
1. B Cell Axis (BTK / BAFF / CD20 / FcRn)
The B cell axis plays a central role throughout the initiation, progression, and maintenance of autoimmune diseases.
In early-stage disease, elevated levels of B-cell activating factor (BAFF, also known as TNFSF13B) allow autoreactive B cells to survive and expand. Subsequently, Bruton’s tyrosine kinase (BTK), a key component of the B cell receptor (BCR) signaling pathway, drives B cell activation, proliferation, and differentiation into plasma cells.
CD20 marks mature B cells, which continuously produce pathogenic autoantibodies. These antibodies form immune complexes that deposit in tissues, triggering inflammation. Meanwhile, neonatal Fc receptor (FcRn) prolongs IgG half-life, sustaining the presence of pathogenic antibodies.
Therefore, this axis represents the “autoantibody production and persistence system”, especially critical in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
1.1 Clinical Breakthrough: ianalumab (Novartis, BAFF-R)
Ianalumab, a BAFF-R-targeting monoclonal antibody developed by Novartis, reported positive Phase III data in Q1 2026 for Sjögren’s syndrome and immune thrombocytopenia (ITP).
Unlike traditional BAFF inhibitors, ianalumab not only blocks BAFF signaling but also depletes B cells via ADCC, achieving dual effects: suppression of new B cell generation, and elimination of existing B cells.
This dual mechanism is particularly impactful in Sjögren’s syndrome, a disease with limited treatment options, demonstrating potential to redefine the standard of care.
1.2 Clinical Breakthrough: obinutuzumab (Roche, CD20)
Obinutuzumab (Gazyva) from Roche achieved its primary endpoint in Phase III trials for SLE, marking a major milestone for CD20 antibodies in lupus. Compared to rituximab, obinutuzumab features glycoengineering enhancements, leading to stronger ADCC and more profound B cell depletion. Consistent improvements in lupus nephritis endpoints validate the concept of deep B cell depletion, bringing CD20 therapies back to the forefront of lupus treatment.
1.3 BD Deal: UCB x Antengene (ATG-201, B Cell Pathway)
In March 2026, UCB entered a collaboration with Antengene worth over $1.1 billion, acquiring autoimmune asset ATG-201. This deal reflects a strategic move: strengthening UCB’s B cell modulation capabilities, and building a comprehensive B cell-targeted portfolio. Big pharma is increasingly constructing “full-spectrum B cell strategies”, covering signaling inhibition to cellular depletion.
2. CAR-T & Cell Therapy (CD19 / BCMA)
CAR-T therapy introduces a paradigm shift in autoimmune diseases by directly eliminating the root cause: pathogenic immune cells.
CD19 is expressed across B cell stages, and CD19 CAR-T enables broad B cell depletion. BCMA (TNFRSF17) is expressed on plasma cells targeting long-lived antibody-producing cells. Unlike conventional therapies, CAR-T can reset the immune system, and potentially achieve long-term remission or functional cure.
2.1 Clinical Breakthrough: miv-cel (Kyverna, CD19 CAR-T)
Kyverna’s miv-cel demonstrated breakthrough efficacy in stiff-person syndrome, including significant reduction in autoantibodies, sustained neurological improvement, and some patients approaching functional cure. A BLA submission is expected in H1 2026, marking CAR-T’s transition into autoimmune indications.
2.2 BD Deal: Eli Lilly x Orna Therapeutics (In Vivo CAR-T)
Eli Lilly acquired Orna Therapeutics for ~$2.4 billion, gaining access to a circular RNA-based in vivo CAR-T platform. This technology enables direct CAR-T generation inside the body, reduced manufacturing complexity, and improved scalability and accessibility. A strategic bet on next-generation autoimmune CAR-T therapies.
3. CD40/CD40L Axis (Immune Co-Stimulation)
The CD40/CD40L pathway is a critical co-stimulatory signal between T cells and B cells. It amplifies immune responses, sustains germinal center reactions, and maintains immune memory. In autoimmune diseases, it acts as both amplifier and sustainer of chronic inflammation.
3.1 Clinical Breakthrough: dapirolizumab (Biogen, CD40L)
Dapirolizumab demonstrated reduced disease activity and lower relapse rates in SLE. Blocking CD40/CD40L enables upstream immune modulation, shifting therapy from cell depletion to immune system rebalancing.
3.2 BD Deal: Sanofi x Kali Therapeutics (KT501 Tri-specific Antibody)
Sanofi partnered with Kali Therapeutics to develop KT501 (CD3×CD19×BCMA). This tri-specific antibody targets multiple immune nodes simultaneously, enhances efficacy, and reduces resistance risk. It represents a shift toward multi-target immunotherapy in autoimmune diseases.
4. FcRn Pathway (IgG Recycling Regulation)
FcRn protects IgG antibodies from degradation, extending their half-life. In autoimmune diseases, this mechanism preserves pathogenic autoantibodies, and sustains chronic inflammation.
4.1 Clinical Breakthrough: nipocalimab (Johnson & Johnson)
Nipocalimab received FDA Fast Track designation in Q1 2026 for SLE. Its mechanism includes blocking FcRn and reducing circulating IgG levels. It offers a non-immunosuppressive strategy with improved safety potential.
5. Innate Immunity & Interferon Axis (BDCA2 / IFN)
The interferon pathway is a key driver in early autoimmune disease. pDCs produce type I interferons (IFN-α), and IFNs activate T and B cells, then creating a self-amplifying inflammatory loop. BDCA2 is a pDC-specific receptor that suppresses IFN production when activated.
5.1 Clinical Breakthrough: litifilimab (Biogen, BDCA2)
Litifilimab targets BDCA2, and suppresses type I interferon production. It has received FDA Breakthrough Therapy designation for SLE, and represents a shift toward early immune intervention strategies.
6. Small Molecule Targets (BTK / JAK / TYK2)
These intracellular kinases regulate immune signaling. Among of them, BTK is involved in BCR signaling; JAK is involved in cytokine signaling (IL-6, IFN); and TYK2 is involved in IL-23 and IFN pathways. Small molecules drugs can block multiple pathways, provide oral treatment options, and enable rapid inflammation control.
6.1 Clinical Progress: remibrutinib (Novartis, BTK)
Remibrutinib is approved for chronic spontaneous urticaria, and expands into autoimmune indications. Its improved selectivity validates BTK as a next-generation oral target.
6.2 BD Deal: Zenas x InnoCare (Multi-target Pipeline)
The collaboration includes Orelabrutinib (BTK), TYK2 inhibitors, and IL-17 antibodies. It reflects a multi-mechanism pipeline strategy, increasing success rates in complex autoimmune diseases.
Beyond classical pathways, emerging targets include IL-17 / IL-23 / APRIL / TNFα, and ICOS / OX40 (T cell co-stimulation). These enable combination therapies, and multi-specific antibody development. They are expected to reshape the future autoimmune treatment landscape.
7. Off-the-Shelf Antibody Sequences for Autoimmune Targets from DIMA BIOTECH
Leveraging its single B cell antibody discovery platform and mammalian display technology, DIMA BIOTECH has developed 5,000+ ready-to-license antibody sequences, covering key autoimmune targets, such as BAFF, BAFFR, CD20, CD19, CD38 and OX40. Most of these sequences include affinity maturation and humanization, and are validated in functional assays. These applications include monoclonal/bispecific/multispecific antibodies development, ADCs and cell therapies. For biotech and pharma companies, this “off-the-shelf antibody licensing model” significantly reduces R&D timelines, lowers development costs, and accelerates pipeline expansion in autoimmune diseases.
